Human Muscle Acetylcholine Receptor Alpha-subunit Gene (CHRNA1) Association with Autoimmune Myasthenia Gravis in Black, Mixed-Ancestry and Caucasian Subjects

• Published in: Journal of autoimmunity Vol. 9; no. 2; pp. 175 - 180
• Main Authors: Heckmann, Jeannine M., Morrison, Karen E., Emeryk-Szajewska, Barbara, Strugalska, Halina, Bergoffen, JoAnn, Willcox, Nicholas, Newsom-Davis, John
• Format: Journal Article Conference Proceeding
• Language: English
• Published: London Elsevier Ltd 01.04.1996; Elsevier
• Subjects: African Continental Ancestry Group - genetics; Biological and medical sciences; Biomarkers; Case-Control Studies; CHRNA1; Diseases of striated muscles. Neuromuscular diseases; ethnic groups; European Continental Ancestry Group - genetics; Humans; Medical sciences; Muscles - metabolism; Myasthenia gravis; Myasthenia Gravis - genetics; Myasthenia Gravis - immunology; Myasthenia Gravis - metabolism; Neurology; Receptors, Cholinergic - genetics; CHRNA1; Myasthenia gravis; ethnic groups; Human; Immunopathology; Neuromuscular diseases; Nervous system diseases; Genetic inheritance; Linkage; Pathogenesis; Repeated sequence; Negroid; Autoimmune disease; Exploration; Striated muscle; Antigen; Allele; Autoantigen; Gene; Microsatellite DNA; Genetics; Alpha-Peptide chain; Acetylcholine; Caucasoid; Biological receptor
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.1996.0021

We have sought associations with the muscle acetylcholine receptor alpha-subunit gene (CHRNA1) in autoimmune myasthenia gravis (MG) patients from three ethnic groups; Caucasians and South Africans of Black and Mixed-Ancestry. We found a significant association with the HB15 CA repeat allele in unrelated Black myasthenics ( n=18; RR=2.85; pX 2=0.04) compared with 52 ethnically matched controls. A family-based association study and linkage analysis in Caucasian simplex and multiplex families supported a positive association at this locus with the longer alleles, including HB*14 to *18. However, no significant cosegregation of the disease with the HB alleles could be demonstrated in affected sib pairs. Our results suggest that the CHRNA1 locus harbours a minor susceptibility gene for developing MG, though we cannot rule out linkage disequilibrium with another major gene locus on chromosome 2.